Kimberly M. Brown

Toxic epidermal necrolysis: does immunoglobulin make a difference?

Experimental evidence implicates Fas ligand-mediated keratinocyte apoptosis as an underlying mechanism of toxic epidermal necrolysis syndrome (TEN). In vitro studies indicate a potential role for immunoglobulin (Ig) therapy in blocking Fas ligand signaling, thus reducing the severity of TEN. Anecdotal reports have described successful treatment of TEN patients with Ig; however, no study to date has analyzed outcome data in a large series of patients treated with Ig using institutional controls. The SCORTEN severity-of-illness score ranks severity and predicts prognosis in TEN patients using age, heart rate, TBSA slough, history of malignancy, and admission blood urea nitrogen, serum bicarbonate, and glucose levels. A retrospective chart review was performed that included all patients treated for TEN at our burn center since 1997. Ig therapy was instituted for all patients with biopsy-proven TEN beginning in January 2000. Twenty-one TEN patients were treated before Ig (no-Ig group), and 24 patients have been treated with Ig. SCORTEN data were collected, as well as length of stay (LOS) and status upon discharge. Each patient was given a SCORTEN of 0 to 6, with 1 point each for age greater than 40, TBSA slough greater than 10%, history of malignancy, admission BUN greater than 28 mg/dl, HCO3 less than 20 mg/dl, and glucose greater then 252 mg/dl. Outcome was compared between patients treated with Ig and without Ig. Overall mortality for patients treated before Ig was 28.6% (6/21), and with Ig, mortality was 41.7%% (10/24). There was no significant difference in age or TBSA slough. The average SCORTEN between the groups was equivalent (2.2 in no-Ig group vs 2.7 in Ig group, P = 0.3), and no group of patients with any SCORTEN score showed a significant benefit from Ig therapy. Overall LOS as well as LOS for survivors was longer in the Ig group. This series represents the largest single-institution analysis of TEN patient outcome after institution of Ig therapy. Our data do not show a significant improvement in mortality for TEN patients treated with Ig at any level of severity and may indicate a potential detriment in using Ig. Ig should not be given to TEN patients outside of a clinical trial. A multicenter, prospective, double-blinded randomized trial is necessary and urgently indicated to determine whether Ig therapy is beneficial or harmful in the care of TEN patients.

Long-term follow-up of patients treated for toxic epidermal necrolysis

Patient outcomes concerning toxic epidermal necrolysis (TEN) have improved over the years as a better understanding of the pathophysiology of the illness has been gained and enhancements have been made in the care of the acutely ill. With increase in survival, long-term complications these patients experience are beginning to be recognized. In this study, we analyzed the outcomes of a cohort of TEN survivors treated at our burn unit and sought to determine the impact of clinical variables from the initial hospitalization on mortality after discharge. We performed a retrospective review of data from patients with TEN treated at our burn unit from March 1993 to September 2002. Follow-up data on new health problems were collected on patients who were alive at discharge via questionnaire. Survival was estimated using the Kaplan-Meier method with Cox regression model. During the study period, of the 64 patients treated for TEN, 46 survived. After discharge, 15 patients died, whereas the remaining 31 patients continued to suffer from ocular (54%), skin (81%), and renal (23%) problems. Median survival for the whole cohort has not been reached, with an estimated 5-year survival of 65%. No patient in either group had a TEN recurrence. Seventy-nine percent of the patients with ocular involvement in the acute phase of TEN had long-term ocular complications, and 73% of patients with mucosal involvement had persistent mucosal lesions. Five individual factors were found to be predictors of postdischarge mortality on univariate analysis: age at diagnosis of TEN ≥ 60 years, SCORTEN 3 to 6, % maximal TBSA slough ≥50%, days from onset of symptoms to admission to a burn unit ≥5 days, and presence of multiple comorbidities at diagnosis of TEN. In multivariate analysis, only SCORTEN of 3 to 6 (P = .003) and days to admission ≥5 (P = .027) maintained significance as predictors of mortality and may be used to heighten surveillance during postdischarge care of patients with TEN.

Central pancreatectomy for benign pancreatic lesions

INTRODUCTION Traditional resections for pancreatic malignancies include distal pancreatectomy with splenectomy and pancrearicoduodenectomy (PD). Alternative resections for benign pancreatic disease are used to minimize the resection of normal pancreatic and splenic parenchyma. This study describes the use of central pancreatectomy (CP) in 10 patients. METHODS A retrospective chart review of all patients undergoing CP between May 1999 and February 2004 was undertaken. RESULTS Ten patients (eight female, two male) underwent CP for benign pancreatic disease. Median age was 59 years (range 21-75). Eight patients presented with abdominal pain, two of whom also had weight loss. One patient each presented with hypoglycemia and as an incidental finding. Median operative time was 255 min (range 160-380 min). Proximal pancreatic remnant was stapled in five and oversewn in five. Distal pancreatic remnant was managed with pancreaticojejunostomy in six patients and pancreatjcogastrostomy in four patients. There were no 30-day mortalities. Pancreatic fistula developed in four patients (40%), and all resolved without operative intervention. All patients are alive with no recurrence and no new endocrine or exocrine dysfunction. CONCLUSION CP has similar morbidity and mortality rates to traditional pancreatic resections and may offer a lower incidence of diabetes and exocrine insufficiency.

Cystic glucagonoma: a rare variant of an uncommon neuroendocrine pancreas tumor

Glucagon-producing neuroendocrine tumors typically present with a characteristic constellation of symptoms including necrolytic migratory erythema, non-insulin-dependent diabetes, weight loss, anemia, glossifis, and an increased thrombotic tendency. Most ghicagonomas are solid and arise in the body or tail of the pancreas. We report two cases of cystic glucagonoma, one found incidentally in an asymptomatic patient and one in a patient with weight loss and diabetes but no rash. In the first patient, distal pancreatectomy and splenectomy were curative, whereas the second patient continued to exhibit elevated serum glucagon levels and symptoms of glucose intolerance in the absence of demonstrable metastases. Cystic glucagonoma is a unique variant of classic glucagonoma and should be considered in the differential diagnosis of cystic pancreatic neoplasms.

The nitric oxide donor molsidomine improves survival and reduces hepatocyte apoptosis in cholestasis and endotoxemia.

BACKGROUND Cholestasis and endotoxemia have been demonstrated to cause hepatocyte apoptosis through caspase-mediated pathways. In vitro nitric oxide (NO) donors reduce hepatocyte apoptosis and caspase activation in several models. The nitric oxide donor molsidomine improves survival in an in vivo model of endotoxemia. We tested the effect of molsidomine on survival and hepatocyte apoptosis in a model of obstructive jaundice and endotoxemia. STUDY DESIGN Sprague-Dawley rats underwent common bile duct ligation on day 1. On day 3, animals were given either 100 mg/kg of molsidomine or an equivalent volume of saline, and 30 minutes later they were given endotoxin 3 mg/kg or 10 mg/kg intravenously. Animals were sacrificed 4 or 16 hours after endotoxin injection. Serum samples were analyzed for alanine aminotransferase and frozen liver samples were analyzed for caspase 3 activity. Paraffin-embedded liver sections were assayed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Survival was measured in a separate experiment in which animals underwent the same protocol, but were given three different doses of endotoxin and were observed for 72 hours before sacrifice. RESULTS At endotoxin 3 mg/kg, the 72-hour survival in saline-treated animals was 92%, which decreased to 45% at 10 mg/kg and to 29% at 15 mg/kg. All of the molsidomine-treated animals survived all endotoxin doses. Alanine aminotransferase was reduced in molsidomine-treated animals compared with those treated with saline. Apoptosis was attenuated in molsidomine-treated animals. Caspase 3 activity was decreased in molsidomine-treated animals compared with those given saline. CONCLUSIONS Molsidomine attenuates caspase activation and hepatocyte apoptosis and improves survival after cholestatic endotoxic injury.